Transmission of cml or of t(9; 22) and bcr/abl? They are not the same

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Transmission of cml or of t(9; 22) and bcr/abl? They are not the same"


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Access through your institution Buy or subscribe In a recent Letter to the Editor de Brito _et al._1 describe a transplant donor retrospectively found to have t(9;22) and _BCR/ABL_ along


with other cytogenetic abnormalities often associated with acute phase or blastic transformation of CML. There are several interesting points including: (1) the donor had normal blood


parameters and no evolution to chronic or acute phase CML for >6 months (but possibly several years) when t(9;22) and _BCR/ABL_ were detected in a substantial proportion of her myeloid


cells; (2) although the donor was chimeric for cells with and without t(9;22) and _BCR/ABL_, initial engraftment was with the normal donor cells; and (3) the recipient did not develop


chronic or acute phase CML after >6 months follow-up. Several points warrant consideration. First, it was reported many years ago that persons with chronic phase CML at diagnosis may have


CML cells with cytogenetic abnormalities consistent with acute phase.2 This is conceptually consistent with recent data from ultra-deep sequencing of the _BCR/ABL_ tyrosine kinase domain in


persons with chronic phase CML, where many mutations are identified before drug exposure.3 These data suggest a long latency from acquisition of _BCR/ABL_ to diagnosis of chronic phase CML.


Second, having _BCR/ABL_ is not equivalent to having CML. Data from several centres report normal persons with _BCR/ABL_.4 The point is that to have CML the _BCR/ABL_ mutation must be in a


cell biologically capable of causing the disease. Whether this was so in this donor (and/or recipient) is unknown. Consequently, starting CML therapy may have been premature and/or


unnecessary, especially absent data-treating chronic phase CML earlier is of benefit. Third, latency from _BCR/ABL_ to developing CML is unknown and likely highly variable. The common notion


derived from the A-bomb survivors of 10–15 years latency is probably wrong. Some children with typical CML, t(9;22) and _BCR/ABL_, were diagnosed before age 1 year and have a somatic


(acquired) mutation implying CML latency can be<2 years. Also, our and other reviews of the A-bomb data suggest an early peak of CML may have occurred<5 years and even<2 years after


exposure.5 Organised surveillance of CML risk did not begin until about 10 years after the A-bomb exposures. More importantly, an increased CML-risk persisted in exposed persons for up to


40 years.6 Based on these data and the ages of donor and recipient, they may never have developed CML in their lifetimes. We do not fault de Brito _et al._ for treating these persons but it


may have been unnecessary. Certainly it would have been interesting to follow these persons to determine if they developed CML. A final point is CML cells do not always have a substantial


growth advantage over normal myeloid cells, which is often used to explain why the chronic phase CML clone eventually displaces (or replaces) normal haematopoietic cells. In this case


initial engraftment was with normal donor cells followed by appearance of cells from the CML clone but no clinical features of CML for >6 months. This is a preview of subscription


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ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * de Brito MD, Campilho F, Branca R, Vaz CP, Campos A . Inadvertent


transmission of occult CML through allo-SCT. _Bone Marrow Transplant_ 2015; 50: 598. Article  CAS  Google Scholar  * Sadamori N, Matsunaga M, Yao E, Ichimaru M, Sandberg AA . Chromosomal


characteristics of chronic and blastic phases of Ph-positive chronic myeloid leukemia. _Cancer Genet Cytogenet_ 1985; 15: 17–24. Article  CAS  Google Scholar  * Soverini S, De Benedittis C,


Machova Polakova K, Brouckova A, Horner D, Iacono M _et al_. Unraveling the complexity of tyrosine kinase inhibitor-resistant populations by ultra-deep sequencing of the BCR-ABL kinase


domain. _Blood_ 2013; 122: 1634–1648. Article  CAS  Google Scholar  * Bose S, Deininger M, Gora-Tybor J, Goldman JM, Melo JV . The presence of typical and atypical BCR-ABL fusion genes in


leukocytes of normal individuals: biologic significance and implications for the assessment of minimal residual disease. _Blood_ 1998; 92: 3362–3367. CAS  PubMed  Google Scholar  * Hsu WL,


Preston DL, Soda M, Sugiyama H, Funamoto S, Kodama K _et al_. The incidence of leukemia, lymphoma and multiple myeloma among atomic bomb survivors: 1950-2001. _Radiat Res_ 2013; 179:


361–382. Article  CAS  Google Scholar  * Radivoyevitch T, Jankovic GM, Tiu RV, Saunthararajah Y, Jackson RC, Hlatky LR _et al_. Sex differences in the incidence of chronic myeloid leukemia.


_Radiat Environ Biophys_ 2014; 53: 55–63. Article  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Experimental Medicine, Department of


Medicine, Haematology Research Centre, Imperial College London, London, UK R P Gale & J F Apperley Authors * R P Gale View author publications You can also search for this author


inPubMed Google Scholar * J F Apperley View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to R P Gale. ETHICS


DECLARATIONS COMPETING INTERESTS The authors declare no conflict of Interest. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Gale, R., Apperley, J.


Transmission of CML or of t(9; 22) and _BCR/ABL_? They are not the same. _Bone Marrow Transplant_ 50, 1582 (2015). https://doi.org/10.1038/bmt.2015.199 Download citation * Published: 14


September 2015 * Issue Date: December 2015 * DOI: https://doi.org/10.1038/bmt.2015.199 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get


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